Session IIB

Monday, May 16th

Session IIB

T15

Towards the
Synthesis of Fluorescent Sensors for Fe(II)

Akanksha Patel and Janet R. Morrow

University at Buffalo, Department of Chemistry

Iron is the
most abundant transition metal found in the body. The accessibility of
different oxidation states including Fe(II), Fe(III) and Fe(IV) makes iron a
useful metal ion for the active sites of metalloenzymes. Consequently, iron is
critical to the function of several biological enzymatic processes.
Dyshomeostasis of cellular iron concentration in the brain has been found in a
variety of neurodegenerative diseases including Alzheimer’s, Parkinson’s,
Huntington’s and multiple Sclerosis. Whether abnormal iron levels are a cause
or an effect of the onset of the disease remains unclear. Current methods to
analyze Fe(II) trafficking in cells are underdeveloped. Fluorescence probes
provide a means to investigate these pathways. Our approach towards this problem
is to develop a fluorescence probe for Fe(II) that produces more intense
fluorescence emission as the metal ion binds (“turn-on”). The design consists
of a binding moiety and a sensing moiety. The binding moiety consists of
macrocyclic ligands which can be functionalized to selectively bind to Fe(II)
in the presence of other biologically relevant ions. The sensing moiety
consists of a fluorophore which emits in visible region. The binding moiety and
sensing moiety are connected via an aryl linker, which is critical towards the
function of a turn on fluorescence probe. Preliminary studies with various
biologically relevant metal ions shows fluorescence quenching in the case of
Zn(II) and Cu(I) binding while an increase in fluorescence intensity was observed
for Fe(II). These results suggest turn on behavior with respect to Fe(II) and
thus shows promise towards the development of a useful fluorescence probe.

The
exploration of renewable energy sources has grown in interest due to the
projected increase in global demand in the coming years. One such renewable
energy source that could supply this demand is solar energy. The use of
dye-sensitized solar cells to harvest solar energy, and the optimization of the
dyes has been widely researched. The synthesis of several new heavy chalcogen
containing dyes for the use in dye-sensitized solar cells will be described.

Malignant
brain tumors, which afflict ~250,000 people annually, are some of the most
aggressive and hard-to-treat cancers. These tumors can be difficult to
eliminate not only because of their rapid growth, but also because their
location may make them inoperable. As a consequence, the development of
effective treatments remains a high priority. Boron neutron capture therapy
(BNCT) is a non-invasive potential treatment for locally invasive malignant
brain tumors. It involves the use of drugs that contain the non-radioactive
isotope boron-10 (10B) which has a high propensity to capture slow neutrons.
Irradiation of the site to which 10B has been introduced results in the
emission of high energy particles that kill the cancer cells. One approach to
the design of biocompatible 10B-containing agents that might have therapeutic
efficacy is to incorporate 10B into scaffolds found in nature, for example,
amino acids, in order to introduce boron into molecules that are likely to be
taken into the cells. Towards the goal of installing a boron-rich moiety into a
biocompatible framework, we synthesized boron containing amino acids, and we
report here on their effects in the immortalized malignant glioma cell line
U87.

Cellular senescence is a state of permanent cell-cycle arrest that
occurs following an extended period of proliferation in culture or in response
to stress. Over the last couple of decades several studies have suggested that
the senescence response evolved as a fail-safe mechanism to protect cells from
cancer. Additionally, senescent cells have been shown to accumulate with age in
human tissues suggesting that senescence may contribute to organismal aging.
Upon entering the senescent state, cells undergo dramatic morphological and
metabolic changes as well as changes in gene expression and protein processing.
The molecular mechanisms underlying senescence have been heavily studied yet we
still have a poor understanding of the role that lipids play in cellular senescence.
In this study, the lipid profiles of proliferating and replicative senescent
fibroblast cells were investigated using liquid chromatography–mass
spectrometry. The comparative analysis of lipid profiles of senescent vs.
proliferating cells allowed us to identify lipids that change during
replicative senescence. Our findings show that there is a specific accumulation
of triacylglycerols, a glycerolipid, in senescent fibroblasts. Our current
efforts are toward elucidation of biochemical mechanisms that are responsible
for these changes. Future work will focus on studying the functional
involvement of the identified triacylglycerols. Gaining a better understanding
of the causes and consequences of senescence may provide novel insights into
how cells react to stress.